Older men are more likely than younger ones to have children with autism or schizophrenia, and a new genetic study points to why: compared with younger dads, older fathers pass on significantly more random genetic mutations to their offspring that increase the risk for these conditions.

And when compared to the genetic contributions of the mother, older fathers are responsible for nearly all of a child’s random genetic mutations: a father’s age at conception may account for 97% of the new, or de novo, mutations found in his offspring, according to the new study led by Augustine Kong at deCODE Genetics in Iceland.

The findings may partly explain the rise in autism diagnoses in recent decades — the rate has reached 1 in 88 children in the U.S. — and they shore up previous studies finding that children born to older dads are more likely to have developmental and psychiatric disorders. The study also counters the common assumption that it is a mother’s advanced age that contributes to these problems. While older mothers are more likely to have children with chromosomal abnormalities, such as Down syndrome, the new study finds that it is the father’s age that accounts for virtually all of the genetic risk of autism and schizophrenia attributable to de novo mutations.

“Our data indicate there is probably much more reason to be concerned with the age of the father,” says Dr. Kari Stefansson, CEO of deCODE and senior author of the paper, published in Nature.

De novo mutations are changes in DNA that arise spontaneously in egg or sperm cells around conception. Most people are born with many such mutations, and most of these changes are harmless. However, some of these mutations have been associated with increased autism risk in previous studies, with that risk rising along with the age of the father.

That makes sense since sperm, unlike women’s eggs, are made constantly throughout a man’s life. With each cell division, the entire genome is copied — and with three billion base pairs packed into 23 pairs of chromosomes, errors can occur in replication. The older men are, the more times his reproductive cells have continuously divided, generating new genetic material — sometimes under environmental exposures such as radiation or other chemical influences that can affect the accuracy with which DNA is replicated. In contrast, a woman’s egg cells don’t divide until they mature in the ovaries.

The study found that a 20-year-old dad passes on an average of 25 new genetic mutations to his child, while a 40-year-old passes 65. For each additional year in the father’s age, children gained two new mutations in their DNA, resulting in a doubling of the de novo mutation rate for every 16.5 years of paternal age. A mother transmits about 15 new mutations, regardless of age.

“It’s not surprising, and makes sense that it is this way,” says Stefansson.

The study involved the sequencing of the full genomes of 78 trios of mother, father and child, in which the children were affected by either autism or schizophrenia but their parents had no mental disorder. The deCODE scientists were thus able to identify new mutations in children’s DNA that didn’t exist in the genetic material of the parents. The researchers also decoded the genomes of 1,859 unrelated Icelanders for comparison, in order to determine which mutations were meaningful and which were background noise.

The analysis showed that while paternal age had a statistically significant effect on mutation rates in children, maternal age did not. The deCODE scientists looked specifically at families affected by autism and schizophrenia because these conditions are caused by a range of mutations, and the researchers were more likely to detect an effect of father’s age with these conditions than with others; brain disorders are likely to be most affected by de novo mutations because more of our active genes play a role in the development of the brain than elsewhere in the body

But while new genetic mutations associated with a father’s age may account for 15% or more of cases of autism, that’s not the full story; at least half of the risk is believed to be due to inherited genes, along with other possible environmental exposures.

The findings also give us insight into how our gene pool is changing, and what, in modern times, is driving the genetic diversity that is critical to the survival of our species. Every difference in our DNA that distinguishes each of us as individuals, or that separates Homo sapiens from other species, arguably got its start as a mutation. Some of these alterations in DNA occur by chance, during cell division, others are triggered by exposure to environmental factors, while still others are selected for when they happen to confer some survival advantage, such as an ability to ward off disease. “It’s extraordinarily important to determine the mutation rate and determine the factors that influence the mutation rate,” says Stefansson. “Mutations are the things that underpin the future diversity of our species.”

The age at which fathers decide to have children may be the driving force behind modern mutation rates, Stefansson and his colleagues found. Indeed, in Iceland, the researchers estimated that children born in 2011 would have 17% more de novo mutations than those born in 1980 (70 mutations versus 60). Over that time period, the average age of fathers rose from 28 to 33.

“It’s basically a compelling connection between the rise in mutation rate and the rise in prevalence of these diseases, [such as autism and schizophrenia],” Stefansson says.

If the findings hold up and the paternal-age effect on the de novo mutation rate is found to affect children’s health broadly, “then collecting the sperm of young adult men and cold-storing it for later use could be a wise individual decision,” wrote Alexey Kondrashov of the University of Michigan in an editorial accompanying the new study.

But other experts say that may not be necessary. Not all such mutations are deleterious, and even the ones that are must occur in the right combinations to generate disease. “The observed effect is a significant one but not one necessarily to cause great worry among prospective older fathers,” Darren Griffin, a professor of genetics at University of Kent, wrote in a comment on the results. “There are three billion of letters in the DNA code of humans and the numbers of mutations detected in this study are in the dozens…and not realistically likely to deter more mature fathers from having children.” It might, however, give them pause before putting off fatherhood for too long.

All the most severe birth defects are linked to the father's age. Half of all cases of Down Syndrome are linked to fathers 40 and over. Most cases of Noonan Syndrome and most cases of mental retardation are now linked to older fathers. Noonans is high risk for men at 50 but what are your odds at 40 or 45? They don't know yet. The father's age is now believed to be much more important to whether a child has Autism Spectrum Disorder. These studies are just the tip of the iceberg for older men. Hopefully, men 40 and over will be adults and admit they are too old to safely father children and put their egos aside. The people who suffer when a man plays a game of craps with his child's health is always the child. And someone always loses.

Nobody is talking about the vaccines. It's not "older fathers". It's in the vaccines-otherwise where are all the late 20 somethings, 30 amp; 40 somethings with Autism? We didn't have the same vaccines used on us but all these new kids and babies are popping up with it like it's normal. It's not.

The metal iron is known to buildup in our bodies as we age. Age-related iron accumulation.

"Iron accumulation in tissues is believed to be a characteristic of aged humans"

Women are less effected because women have menses which allow them to lose much of this iron , until they reach menopause , at which point they begin to load iron JUST like men because they no longer lose the iron in their monthly blood loss .

"Women have lower iron levels than men, both in the periphery and in the brain, particularly in white matter (WM), possibly due to iron loss through menstruation"

Men though have no way to lose this iron. This 'age-related iron accumulation' causes rust / oxidation which causes mutation.

I do not believe this story one bit, it is totally bad science. In addition, considering the so- TV generation losers of "Young men" today(hooked on video games and so called adult cartoons like "family guy") I would rather a mature older man over any loser under 35 with great abs.

"The findings may partly explain the rise in autism diagnoses in recent decades — the rate has reached 1 in 88 children in the U.S."

===

While autism is on the rise, that 1 in 88 figure is largely the result of over-diagnosis. They're using "autism" as an umbrella term, just like they used "consumption" in the 18th century as an umbrella term for all wasting diseases.

In one case, you might have a child of six who has never spoken or communicated. He does not respond to his name. He doesn't play with other children. He obsessively stacks blocks for hours, and without anything to do, he rocks and hums. That's autism.

Then you have a child of the same age who's loud. He has no trouble communicating but has problems with impulse control. He plays normally with other children, but is a frequent discipline problem because he's excitable, energetic, and doesn't listen. And they tell you he has autism too.

Like hell. "Oh, it's a spectrum," they say. Bull. If two people with so different symptoms have the same condition, the condition needs to be more specific. This isn't the 18th century.

More older men are using drugs for erectile disfunction those drugs could be the cause as the body would naturally shut down without the drugs and prevent unhealthy offspring from being born. In other words, don't force the issue if your body is telling you not to.

First, its not a disease, its a neurological difference. Comparing autism to consumption not only makes no sense, but its demeaning and furthers the bigoted agenda of organizations Austism Speaks (who believes that austism is a horrible disease and all autistic people need to be 'cured' )

Second, the problem is not us (autistic people), its society.

Western society has decided to put children into schools that want complete conformity and do not make allowance for individual differences or needs. Western society has decided to put workers into cubicles and measure all employees by metrics and productivity formulas.

Now you have to slap labels like ADHD, learning disabilities, and autism on those who don't fit into the assembly line process. I know this is a radical thought, but even if we do come up with a miracle 'cure' for those of us who don't fit into this brave new society, what are you going to do about those who are conforming? You know all those in Western society who are now suffering from the current epidemics of obesity, heart problems, and mental illness?

the body would naturally shut down without the drugs and prevent unhealthy offspring from being born. In other words, don't force the issue if your body is telling you not to. http://HopsonToday5.blogspot.c...

Interesting point, but the article specifically mentioned changes that occurred between the ages of 20 and 40. I'd be surprised if a significant number of men in that age group are taking ED drugs. I don't think people having children in their 30s is really new or radical. It's people having their FIRST babies after 30 that seems to be the rising trend.